ABSTRACT
A new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.
Subject(s)
Acute Coronary Syndrome/diagnosis , Anticoagulants/administration & dosage , Cell Adhesion Molecules/metabolism , Enzyme-Linked Immunosorbent Assay/methods , Microfilament Proteins/metabolism , Phosphoproteins/metabolism , Piperazines/administration & dosage , Thiophenes/administration & dosage , Ticlopidine/analogs & derivatives , Acute Coronary Syndrome/blood , Aged , Cell Separation , Clopidogrel , Feasibility Studies , Female , Flow Cytometry , Humans , Male , Middle Aged , Platelet Function Tests , Prasugrel Hydrochloride , Reference Standards , Reproducibility of Results , Sensitivity and Specificity , Ticlopidine/administration & dosageABSTRACT
It was the objective of this study to assess the effect of the implementation of the smoke-free legislation on haemostasis and systemic inflammation in second-hand smoking (SHS)-exposed healthy volunteers. Fibrin-rich clot properties, platelet reactivity and inflammatory biomarkers were measured before and four months following the implementation of the smoke-free legislation in gender and age-matched healthy volunteers exposed (n=23, exposed) and unexposed (n=23, controls) to occupational SHS. The primary objective was to compare fibrin-rich clot stiffness before and after implementation of the smoke-free legislation. There was 40% reduction in fibrin-rich clot stiffness following the implementation of the smoke-free legislation in SHS-exposed volunteers (17 ± 7 vs. 10.6 ± 7 dynes/cm², before and after, respectively, p=0.001). These dramatic changes were associated with a 20% reduction in fibrin fiber density (p<0.01) and a 20% reduction in clot lysis time (p=0.05). No change in fibrin properties was observed in the control group of SHS-unexposed volunteers related to the implementation of the smoke-free legislation. Of interest, neither platelet reactivity nor systemic inflammatory biomarkers were changed in either group. The smoke-free legislation is associated with significant changes in fibrin-rich clot properties toward a less thrombogenic conformation with a better fibrinolysis response while neither platelet reactivity nor systemic inflammatory biomarkers are modified. These improvements may explain the observed reduction in acute coronary syndrome following the implementation of the smoke-free legislation.
